tbuckley/cabot-search huggingface dataset:
Abstract 13833: Arrhythmia Patterns in Patients Managed With and Without Tyrosine Kinase Inhibitors
Authors: Chen Wei, Muhammad Fazal, Ridhima Kapoor, Paul Cheng, Albert J Rogers, Alexander C Perino, Sanjiv M Narayan, June W Rhee, Tina Baykaner
Journal: Circulation (2022)

Introduction: Tyrosine kinase inhibitors (TKIs) are often used to treat hematologic malignancies. Ibrutinib, a Bruton’s TKI, has been associated with increased burden of treatment limiting arrhythmias. How this compares to arrhythmias in patients on non-ibrutinib TKIs or non-TKI therapy is unknown. Hypothesis: We hypothesized that ibrutinib therapy would be associated with higher atrial and ventricular arrhythmia burden than non-ibrutinib TKI or non-TKI therapies in patients with hematologic malignancies. Methods: We performed a retrospective single center chart review of consecutive patients who received 14-day cardiac event monitors while on ibrutinib, non-ibrutinib TKIs, or non-TKI therapy for a hematologic malignancy between 2014-2021. Results: A total of 176 patients were included (ibrutinib=72, non-ibrutinib TKI=36, non-TKI=68; Figure A). The ibrutinib group had higher incidence of AF (n=32, 44%) and NSVT (n=31, 43%) than the non-ibrutinib TKI (AF: n=7, 19%, p=0.02; NSVT: n=8, 22%, p=0.03) and non-TKI group (AF: n=13, 19%, p=0.003; NSVT: n=14, 21%, p=0.006; Figure B). Rates of SVT, PAC burden, and PVC burden were not significantly different. Therapy was held in 25% (n=18) of patients on ibrutinib vs 5% (n=2) on non-ibrutinib TKIs. Average duration of TKI therapy was 32 months in the ibrutinib group vs 77 months in the non-ibrutinib group (p&lt;0.001). Of note, the non-TKI group had significantly higher outpatient cardiology follow-up versus the TKI groups (p=0.048). Conclusions: In this large retrospective comparison of cardiac event monitors in patients with hematologic malignancies on ibrutinib, non-ibrutinib TKIs, or non-TKI therapy, those receiving ibrutinib had a higher incidence of atrial and ventricular arrhythmias and higher rate of treatment interruption due to arrhythmia burden but less cardiology follow-up. Further research is needed to optimize risk stratification, surveillance, and management of TKI-related arrhythmias.
Abstract 14195: The Effects of Pulmonary Capillary Wedge Pressure (PCWP) Reduction on Starling Mechanisms in Heart Failure With Preserved Ejection Fraction (HFpEF): Potential for Harm?
Authors: Seamus B Hughes, Denis J Wakeham, Joetsaroop S Bagga, James P Macnamara, Bryce N Balmain, Christopher M Hearon, Tony G Babb, Benjamin D Levine, Satyam Sarma
Journal: Circulation (2022)

Introduction: Elevated left ventricular (LV) filling pressure during exercise is a pathognomonic characteristic of HFpEF. Multiple therapies aiming to reduce filling pressures in HFpEF patients have failed to improve exercise capacity and in some studies, decreased activity levels. The Dynamic Starling Mechanism (DSM) quantifies beat-by-beat modulation of stroke volume (SV) by respiratory-mediated changes in LV filling and provides insight into the efficiency with which changes in LV filling pressure are converted to SV. Low DSM gain reflects inefficient conversion of LV pressures (input) into stroke volume (output). In this study, we examined the effect of sublingual nitroglycerin (NTG; 400μg given q15 minutes) to lower PCWP compared to placebo on DSM. Methods: HFpEF patients (n=11, 7 women; age 73 ± 7 years) were studied seated upright at rest following sublingual administration of placebo or NTG. DSM was quantified by transfer function analyses of beat-by-beat changes in pulmonary artery diastolic pressure (PAD, right heart catheterization as index for PCWP) and SV (Modelflow from radial arterial line waveform, normalized to direct Fick-derived SV) at the prevailing respiratory frequency. Direct Fick SV was calculated as VO2/a-vO2 difference divided by heart rate. Results: Compared to placebo, NTG decreased both SV (Placebo: 53 ml vs NTG: 43 ml, p=0.004) and PAD (Placebo: 15.0 mmHg vs NTG: 13.9 mmHg, p=0.026). The DSM gain was decreased with NTG compared to placebo (0.57 vs 0.82 ml/mmHg, p&lt;0.0001) suggesting a smaller change in SV for a change in filling pressure. Conclusions: Lowering cardiac filling pressures in the seated upright position decreased efficiency of the beat-by-beat Starling mechanism. The results may provide insight into how reducing LV filling pressures impacts stroke volume regulation, potentially leading to decreased exercise tolerance in HFpEF patients.
Abstract 13442: Right Ventricular Outflow Tract Doppler Notching: A Sensitive Non-Invasive Discriminator of Pulmonary Vascular Disease in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Gregory S Troutman, Priyanka T Bhattacharya, Edo Y Birati, Payman L Zamani, Stuart B Prenner, E. Wilson Grandin, Jonathan N Menachem, Steven M Kawut, K. Akaya Smith, Paul R Forfia, Anjali Vaidya, Jeremy A Mazurek
Journal: Circulation (2022)

Introduction: Pulmonary hypertension (PH) in the setting of heart failure with preserved ejection fraction (PH-HFpEF) is further characterized as isolated post-capillary PH (IpcPH) or combined pre- &amp; post-capillary PH (CpcPH). This is distinguished by pulmonary vascular resistance (PVR) cut-off of 3 WU. Prior definitions used a diastolic pulmonary gradient (DPG) cut-off of 7mmHg to distinguish PH subtype. Studies have examined echocardiographic right ventricular outflow tract Doppler notching (RVOT-notch) as a correlate for pulmonary vascular disease, though its role in distinguishing PH-HFpEF subtype by current vs. prior definition has never been described. Hypothesis: Our study explores the ability of RVOT-notch to distinguish CpcPH from IpcPH in patients with PH-HFpEF, in the context of current PVR &amp; prior DPG cutpoints. Methods: We retrospectively reviewed patients with PH-HFpEF referred to our PH program who underwent right heart catheterization and echo (later reviewed independently by blinded cardiologists to assess RVOT-notch). Results: 86 patients with PH-HFpEF were reviewed with a mean age of 66 and female predominance. Patients with RVOT-notch had signs of worsening right heart function both via echocardiography (higher estimated PASP, more severe TR, lower TAPSE) &amp; hemodynamically (higher DPG, higher PVR, and lower pulmonary arterial compliance). RVOT-notch was able to distinguish CpcPH from IpcPH, with current PVR cut-off ≥3 WU (sensitivity 91%, specificity 68%, PPV 76%, NPV 88%) and prior DPG cut-off ≥7mmHg (sensitivity of 94%, specificity 58%, PPV 57%, NPV 94%). Conclusions: In PH-HFpEF, RVOT-notch is a sensitive marker of CpcPH, and notably better reflects the current PVR-based definition (PVR≥3) with better specificity than prior DPG-based definition. This could have implications as non-invasive screening for CpcPH in patients with PH-HFpEF. Further work is needed to validate this marker in larger cohorts.
Abstract 13344: Endothelin B Receptor Agonist, Sovateltide, Promotes Neural Regeneration by Improving Mitochondria Function in a Neonatal Rat Model of Hypoxic-Ischemic Encephalopathy
Authors: Seema Briyal, Sarah Hurrell, Preetha Prazad, Anil Gulati
Journal: Circulation (2022)

Introduction: Our preliminary studies have indicated the role of Endothelin B receptors (ETBR) stimulation in decreasing oxidative stress and cell death after sovateltide treatment following hypoxic-ischemic encephalopathy (HIE) in rat pups, which suggests the involvement of ETBR in neonatal hypoxic-ischemic injury. However, its mechanism of action is not yet established. Therefore, this study investigated the effect of sovateltide on mitochondrial dysfunction and neurogenesis in a neonatal rat model of HIE. Hypothesis : Sovateltide protects neuronal survival via preserving mitochondrial activity. Methods: Sprague-Dawley male and female rat pups grouped separately, were divided into 5 different subgroups (1) Control; (2) HIE + Vehicle; (3) HIE + Hypothermia; (4) HIE + sovateltide; and (5) HIE + sovateltide + hypothermia. HIE was induced by ligating the right carotid artery on a postnatal day (PND) 7, followed by hypoxia for 120 min and hypothermia (32-34°C) for 5 h. On PND 7, sovateltide (5 μg/kg, ICV) was injected after hypoxic-ischemic injury. Pups were euthanized on PND 10. Brains were isolated for analysis of markers for mitochondrial fission and fusion as well as neurogenesis in rat brain tissues using western blots. Results : Animals receiving sovateltide showed a significantly increased expression of neuronal differentiation marker, NeuroD1 (p&lt;0.0001) and DoubleCortin (p&lt;0.001) along with neural marker for mature neurons, NeuN (p&lt;0.001) compared to vehicle. Additionally, an upregulation (p&lt;0.0001) of mitochondrial fusion-related proteins, Mfn2, and downregulation of fission proteins, Drp1, in the sovateltide group compared to the vehicle was observed. Higher neuronal progenitor cell differentiation along with better mitochondrial biogenesis in the brain of sovateltide alone or as an adjunct to hypothermia in rat pups was noted. Similar findings were obtained in both male and female rats. Conclusion : Stimulation of ETBR by sovateltide promotes neural regeneration via maintaining mitochondrial dynamics, indicating a potential neuroprotective effect and may, therefore, offer a legitimate therapeutic target for the treatment of neonatal HI brain injury.
Abstract 141: Associations Between Sex Steroids And Cardiac Arrest Outcomes
Authors: Pavitra Kotini-Shah, Ruth Pobee, Irina Buhimschi, Benjamin Karfunkle, Misha Granado, Terry L Vanden Hoek, Jing Li
Journal: Circulation (2022)

Introduction: Sudden cardiac arrest (SCA) is one of the leading causes of death in both males and females although females tend to have better outcomes. While sex steroids influence cardiovascular disease, and low level of testosterone and high level of estradiol is associated with the risk of SCA, little is known about their changes after a cardiac arrest, and their association to outcomes. We sought to characterize the temporal trajectories in sex steroids (estrogens [estrone and estradiol], progesterone, and testosterone) in the post-return of spontaneous circulation (ROSC) phase and determine associations with survival and neurological outcomes. Hypothesis: Sex steroids and their temporal trajectories post-SCA are associated with survival and neurological outcomes. Methods: Plasma samples from SCA patients (n=65, 74% males) were collected at the University of Texas Houston between May 2018-March 2020 at four serial time points (0, 6, 24, 48h) post-ROSC. Quantitative sex hormone analysis was performed using LCMS. Data was analyzed by t-test, Chi 2 test and Generalized Estimating Equation (GEE) with p&lt;0.05 indicating significance. Results: There were no differences in demographic and clinical characteristics between males and females. Plasma estrogens peaked at 24 hours, whereas progesterone and testosterone peaked at 6 hours. Estrogens and testosterone were higher in males, while progesterone trended higher in females. Hormonal trajectories did not differ by survival, however, testosterone concentrations were lower in patients with good neurological recovery. Lower estradiol was associated with survival (β: -13.80, p=0.016) adjusting for sex, time, and age, while a lower testosterone was associated with good neurological recovery (β: -0.68, p=0.031) adjusting for time. Conclusion: Increased circulating sex steroid concentrations were observed in the post-ROSC phase after SCA. High levels of estrogens were associated with worse survival independent of sex, and lower testosterone levels were associated with better neurological recovery. A larger sample size and simultaneous measurement of cortisol will be important to better understand the role of sex hormones in outcomes after SCA.
Abstract 14187: Neighborhood Walkability and Cardiovascular Risk in the United States
Authors: Issam Motairek, Mohamed H.E. Makhlouf, Khurram Nasir, Salil V Deo, sanjay Rajagopalan, Sadeer Al-Kindi
Journal: Circulation (2022)

Walkability may be associated with increased physical activity and thus may confer protection against cardiovascular disease and associated risk factors. We sought to characterize the association between neighborhood-level cardiovascular diseases and risk factors with neighborhood walkability across most US census tracts. Methods: The Centers for Disease Control and Prevention (CDC) PLACES dataset provided census-tract level prevalence of coronary artery disease (CAD) and cardiovascular risk factors (hypertension, high cholesterol, obesity, and diabetes). These data were matched with census tract population-weighted walkability index from the CDC’s smart location database. We calculated the mean prevalence of each cardiovascular health indicator by quartile of walkability score. We also fit a multivariable linear regression model to estimate the association between walkability index and the prevalence of CAD adjusting for age, sex, race, and the CDC'S social vulnerability index, a validated metric of socioeconomic status. Results: 70,123 census tracts were analyzed nationwide. Across walkability quartiles Q1 (least walkable) through Q4 (most walkable), we found a statistically significant decrease in the prevalence of CAD (7.0% to 5.4%). Similarly, there was a decrease in the prevalence of CVD risk factors including hypertension (35.5% to 29.7%), high cholesterol (34.5% to 29.7%), obesity (35.0% to 30.2%), and diabetes (11.6% to 10.6%) across walkability quartiles ( Figure ). After multivariable adjustment, continuous walkability index was negatively and significantly associated with the prevalence of CAD (β = -0.09, p &lt; 0.0001). Conclusions: This nationwide analysis demonstrates that neighborhood walkability is associated with a lower prevalence of cardiovascular risk factors and CAD. Figure: Mean prevalence of cardiovascular health indicators according to walkability index quartile. BP = blood pressure, CAD = coronary artery disease.
Abstract 12852: Transcatheter Aortic Valve Replacement for Aortic Stenosis in Small Aortic Annulus: Medium-Term Follow-Up
Authors: Artemio Garcia Escobar, Silvio Vera, Daniel Tébar, Alfonso Jurado, Santiago Jiménez, Galeote Guillermo, Raúl Moreno
Journal: Circulation (2022)

Introduction: Small aortic annulus (SAA) is a clinical challenge in managing aortic stenosis (AS). The SAA has been associated with poorer outcomes after surgical AVR with an increased risk of perioperative and overall mortality, suboptimal valvular hemodynamics, and adverse cardiovascular events. Hypothesis: TAVI could be a therapeutic alternative in these patients. Methods: We performed a retrospective analysis of all patients with AS treated with TAVI from 2015 to 2021 in our center, with SAA defined as the aortic annulus of ≤22mm perimeter-derived diameter (PDD), measured by CT. Results: Sixty-eight patients were included (85.3% women, 83.2± 6.5 years) with a mean PDD of 20.7 ± 1.1 mm. The 14.7% had LVEF &lt;50% and 1.4% had bicuspid aortic valve. The Access route was transfemoral in 64 patients (94.2%) and 4 transapical (5.8%). Self-expanding prostheses were used in 78% of the cases, balloon-expandable prostheses in 17.6%, and mechanically-expandable prostheses in 4.4%. The size of the aortic prostheses was 23mm in 82.3% and &gt;23mm in 17.7%. The perioperative implant success rate was 100% defined as single prosthesis implantation with a mean gradient &lt;20mmhg and angiographic paravalvular leak &lt;2. The rate of new permanent pacemaker implantation was 13.2%. The in-hospital complications rate was 5.8% (4 patients): major vascular complication in 1 patient (1.4%), acute kidney injury stage ≥2 in 1 (1.4%), disabling stroke in 2 (2.9%). There were no deaths in the first 30 days of the procedure. At discharge, the TTE máximum gradient was 19.8 ± 9.2mmhg, the mean gradient 9 ± 4.8mmhg, and 4 patients had paravalvular leak grade ≥2 (5.9%). During a mean follow-up of 27.8 ±7.6 months, 45 patients were in NYHA functional class I (66.2%), 19 in NYHA 11 (27.9%), and 3 in NYHA III (4.4%). Eight patients (11.7%) were readmitted due to heart failure, 10 died (14.7%) due to all-cause mortality, and only 3 of them died due to cardiovascular causes (4.4%). Conclusions: Although the optimal approach for treating patients with AS and SAA remains controversial. TAVI is a very attractive option in these patients, allowing the implantation of prostheses with excellent immediate hemodynamic results, a low rate of complications, and significant clinical improvement in the follow-up.
Abstract 14796: Fifteen-Year Trend in Antiplatelet Treatment Among Drug-Eluting Stent Recipients: Newer Drugs Are Replacing the Older Ones
Authors: Sunwon Kim, Jong-Seok Lee, Woo Hyuk Song
Journal: Circulation (2022)

Backgrounds: Drug-eluting stent (DES) recipients require 6-12-month P2Y12 inhibitor (P2Y12i)-based dual antiplatelet treatment (DAPT) and long-term aspirin mono antiplatelet treatment (MAPT). Given the diversity of contemporary antiplatelet agents, antiplatelet treatment (APT) selection is becoming more complicated in this patient population. Herein, we evaluated 15-year APT trends among DES recipients nationwide. Methods: Nationwide prescription data of 79,654 patients who underwent percutaneous coronary intervention (PCI) using DESs from 2002 to 2018 in Korea were analyzed. APT claim data were collected longitudinally at multiple time-points post-PCI. Fifteen-year longitudinal APT pattern changes were analyzed at 3-year intervals. Results: DAPT (80.7%) was the most preferred initial APT, followed by MAPT (7.8%) at 3 months post-PCI. A substantial number of patients received prolonged DAPT post-PCI (3 years: 41.0%; 10 years: 27.7%). There was a noticeable delay in DAPT-to-MAPT conversion from the mid- to late-2000s; the conversion was similar during the 2010s, occurring most robustly at 12-18 months post-PCI. Clopidogrel had long and increasingly been used for long-term MAPT, surpassing aspirin from 2013-2015. Recent increases in newer P2Y12i (mostly ticagrelor) prescription were noted. However, P2Y12i use was still low (2013-2018: 25.8%) and peaked immediately post-PCI. The patients treated with newer P2Y12is were more likely younger men and presented with acute myocardial infarction, suggesting that physician-directed newer P2Y12i use remained limited to patients with low bleeding risks. Conclusions: Real-world APT is evolving, however guideline-practice gaps exist. Newer drugs were replacing the older ones, even challenging role of aspirin as chronic maintenance monotherapy. Further studies exploring the impact of diverse APT strategies on patient outcomes are expected to provide insights into optimal APT that can sophisticatedly balance the ischemic and bleeding risks.
Abstract 13094: Extracellular Vesicles Associate With Cardio-Metabolic Status and Endothelial Dysfunction in a Cohort of African-American Women
Authors: Noel Miller, Yvonne Baumer, Matthew Bavuso, Ruben Manuel Luciano Colunga Biancatelli, Valerie Mitchell, Billy Collins, Tiffany Powell-Wiley, Anca Dobrian
Journal: Circulation (2022)

Extracellular vesicles (EVs) are emerging as promising biomarkers for cardiovascular disease (CVD) and contributors to CVD pathogenesis. Plasma EVs access the endothelium from various vascular beds allowing them to impact endothelial function and inform on the global particulate secretome produced by parenchymal, vascular and immune cells. In this study we examined associations between plasma EVs and biochemical and physiological parameters in a cohort of African American (AA) women at risk for CVD. We also examined EV effect on coronary endothelial function. This study will serve as baseline data for a longitudinal study aimed to determine the effects of exercise on EVs and endothelial function in a similar cohort.A cohort of 24 AA women between 22-71 yrs, with BMI between 26-47 kg/m 2 and ASCVD risk scores between 2.3-22.1 were included in the study. EVs were isolated from fasted heparinized plasma using size exclusion chromatography. EV size and numbers were determined using nanoparticle tracking analysis. Lipids, inflammatory cytokines, and metabolic panels were measured at the time of blood draw. Human coronary endothelial cells were treated with EVs from participants and endothelial barrier function and migration were measured using ECIS technology. Associations were determined using multivariable linear regression analysis, adjusted for BMI and ASCVD risk.We found a negative association (beta=-0.712, p&lt;0.01) between total triglycerides (TG), TG rich lipoprotein (Lp), and EV size; EV concentration was positively associated (beta= 0.51-0.61, p&lt;0.01) with TG rich Lp, LDL cholesterol and TNFa. Reduced endothelial barrier function due to EVs was positively associated with monocyte counts (beta=0.42, p&lt;0.05). EVs effect on increased endothelial migration was strongly and negatively associated with monocyte counts (beta=-0.85, p&lt;0.001), IL8 and CXCl10 (beta=-0.56-0.46, p&lt;0.05).Collectively these data show that EVs number and size strongly associate with circulating lipids, while EV impact on endothelial dysfunction is associated with inflammatory markers. EVs are therefore promising indicators of endothelial dysfunction that associate with inflammatory and metabolic markers even after adjusting for BMI and ASCVD risk.
Abstract 14258: Left Bundle Branch Pacing for Cardiac Resynchronization Therapy in Heart Failure: A Systematic Review and Meta-Analysis
Authors: Mahmoud El Iskandarani, Islam Shatla, Mohamad Kassab, Marwan M Refaat, Timir K Paul
Journal: Circulation (2022)

Introduction: : Cardiac resynchronization therapy (CRT) using a biventricular pacemaker (BVP) reduced mortality and rehospitalizations in patients with symptomatic heart failure (HF) with a left ventricular ejection fraction (LVEF) of less than 35% and concomitant left bundle branch block. However, 10-30% of BVP patients fail to show a clinical or echocardiographic response. Recently left bundle branch pacing (LBBP) has been studied as a more physiological alternative to BVP. The aim of this study is to summarize the available evidence on LBBP. Hypothesis: LBBP is an effective and feasible alternative option for CRT. Methods: Unrestricted searches of the PubMed, EMBASE, and Cochrane databases from inception till June 1, 2022, for studies examining the role of LBBP for CRT in HF patients. Data were analyzed using Revman 5.3 software. Mean Difference (MD), Odds Ratio (OR), and 95% Confidence interval (CI) were calculated using the random-effects model. Results: A total of 8 observational studies (3 single-armed, and 5 comparative studies) examined 756 HF patients who underwent CRT (551 LBBP vs 205 BVP). LBBP was successful in 87% of patients. Compared to baseline, LBBP was associated with a reduction in QRS duration (MD -53.5, 95%CI -69.77, -37.24), an increase in LVEF (MD 17%, 95%CI 13.38, 20.6), and a reduction in NYHA class (MD -1.4, 95%CI -1.56, -1.05). Compared to BVP, LBBP was associated with a significant reduction in QRS duration (MD -22.68, 95%CI -31, -14.35), improvement in LVEF (MD 7.58, 95%CI 5.21, 9.95), and a decrease in NYHA class (MD -0.55, 95% CI -0.73, -0.37) during a mean follow-up of 9.2 months. The super response rate, which is defined as an increase in LVEF of more than 20% or LVEF at or above 50% after CRT, was higher in LBBP compared to BVP (OR 2.98, 95%CI 1.65, 5.32). Conclusions: LBBP is a feasible and effective alternative for CRT. LBBP was associated with better electrical ventricular synchrony than BVP which was also translated into better echocardiographic and clinical outcomes in the short term. Our findings need to be further validated in larger randomized controlled trials with a long-term follow-up.